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Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo -Lactamase-1

1
Pharmaceutical Sciences Division, University of Wisconsin–Madison, Madison, WI 53705, USA
2
Department of Biosciences, Rice University, Houston, TX 77005, USA
3
Department of Chemistry, Rice University, Houston, TX 77005, USA
4
Department of Medicine, University ofWisconsin School of Medicine and Public Health, Madison, WI 53705, USA
*
Author to whom correspondence should be addressed.
Mar. Drugs 2020, 18(6), 295; https://doi.org/10.3390/md18060295
Received: 23 April 2020 / Revised: 22 May 2020 / Accepted: 25 May 2020 / Published: 2 June 2020
(This article belongs to the Special Issue Fighting Antimicrobial Resistance with Marine Antibacterial Compounds)
Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo--lactamase (NDM) enzymes are a contributing element that drive resistance to many -lactam- and carbapenem-based antimicrobials. Many NDM inhibitors are known, yet none are clinically viable. In this study, we present and characterize a new class of NDM-1 inhibitors based on a pyridine-2,6-dithiocarboxylic acid metal complex scaffold. These complexes display varied and unique activity profiles against NDM-1 in kinetic assays and serve to increase the effectiveness of meropenem, an established antibacterial, in assays using clinical Enterobacteriaceae isolates.
Keywords: NDM-1 inhibitors; marine-derived Streptomyces sp.; carbapenem-resistant Enterobacteriaceae; metal chelators NDM-1 inhibitors; marine-derived Streptomyces sp.; carbapenem-resistant Enterobacteriaceae; metal chelators
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MDPI and ACS Style

Thomas, C.S.; Braun, D.R.; Olmos, J.L., Jr.; Rajski, S.R.; Phillips, G.N., Jr.; Andes, D.N.; Bugni, T.S., Jr. Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo -Lactamase-1. Mar. Drugs 2020, 18, 295.

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